title: Candida parapsilosis fat storage-inducing transmembrane (FIT) protein 2 regulates lipid droplet formation and impacts virulence.
abstract: Neutral lipid storage in lipid droplets (LDs) is a conserved process across diverse species. Although significant attention has focused on LDs in the biology of obesity, diabetes, and atherosclerosis, there is limited information on the role of LDs in pathogenic fungi. We have disrupted the Fat storage-Inducing Transmembrane (FIT) protein 2 genes of the emerging pathogenic fungus Candida parapsilosis and demonstrated that LD formation is significantly reduced in the mutant cells. Disruption of FIT2 genes also reduced accumulation of triacylglycerols. The production of other lipids such as phospholipids and steryl esters were also affected in the mutant strain. Inhibition of de novo fatty acid biosynthesis by triclosan in the FIT2 disruptants reduced fungal growth in rich medium YPD, indicating that TAGs or fatty acids from the LDs could be important for cell proliferation. FIT2 disruption was associated with enhanced sensitivity to oxidative stress. Furthermore, we showed that FIT2 deletion yeast cells were significantly attenuated in murine infection models, suggesting an involvement of LDs in the pathobiology of the fungus.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine, New York, NY 10461, USA.
authors.forename: Long N
authors.initials: LN
authors.lastname: Nguyen
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Hamari
authors.forename: Bert
authors.initials: B
authors.lastname: Kadereit
authors.forename: David
authors.initials: D
authors.lastname: Trofa
authors.forename: Mariangela
authors.initials: M
authors.lastname: Agovino
authors.forename: Luis R
authors.initials: LR
authors.lastname: Martinez
authors.forename: Attila
authors.initials: A
authors.lastname: Gacser
authors.forename: David L
authors.initials: DL
authors.lastname: Silver
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Nosanchuk
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000935:Antifungal Agents / Q000378:metabolism; D002175:Candida / Q000235:genetics* / Q000472:pathogenicity*; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008805:Mice, Inbred A; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014260:Triclosan / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D014774:Virulence
chemical_list: D000935:Antifungal Agents; D005227:Fatty Acids; D005656:Fungal Proteins; D008565:Membrane Proteins; D014280:Triglycerides; D014260:Triclosan